The overall objective of the Program is to understand how chronic inflammation contributes to tumor promotion and progression. The current program will address several aspects of injury/pathogen-initiated signaling pathways focusing upon TLRs, the involvement of altered transcriptional and post-transcriptional control, and the causal links between inflammatory signaling and neoplasia. A major component that links three of the projects involves much expanded utilization of mouse genetics and mouse models of inflammatory disease and carcinogenesis. In each of project 1, 3 and 4, new transgenic mice will be generated, characterized and tested in several models of in vivo inflammatory response. A central focus of these studies will be the use of the mouse model of DSS colitis and its linkage with colon tumorigenesis. This central activity will be coordinated by the newly propose Core B (Mouse Colitis and Colitis-associated Cancer Analysis Core). The colitis analysis portion of this Core's primary objective is to set up a colitis model induced by DSS, TNBS or adoptive transfer and provide technical assistance in the analysis of the colitis symptoms, states of homeostasis and inflammation induced in transgenic mice produced by projects. The colitis-associated cancer portion of this core's primary objective is to set up the AOM+DSS-induced CAC model and provide specific technical assistance in phenotype analyses (including tumor number, tumor size, histology analysis and other assays). Standardization of the protocols, evaluation and quantitative assays of colitis and tumorigenesis will facilitate inter-laboratory collaboration and data comparisons.